This research proposal is a multidisciplinary approach to characterize the biologic actions of acrylonitrile and to gain insight into its mechanism of action. The acute and chronic toxicity of acrylonitrile, and its saturated analog, propionitrile, will be studied in rats, mice, guinea pigs, hamsters and rabbits by using LD50 determinations, gross, light and electron microscopic observations, as well as biochemical and physiological measurements. The chemicals will be administered p.o. (gavage), i.v. or inhalation in acute experiments; and put in drinking water or by inhalation in chronic assays. Specific attention will be placed on the neuroendocrine, gastrointestinal and pulmonary systems. The carcinogenic potential will be sought in male rats kept for 1, 2 or 3 years on drinking water containing acrylonitrile and Purina Lab Chow or lipotrope-deficient diets which were shown to enhance the tumorigenic action of several chemical carcinogens. The site of injury and severity of lesions will also be investigated after induction of mixed function oxidase, by diets, and by modification of hormonal states of animals. An important part of the project will be the identification of metabolites and tissue and subcellular distribution of radiolabelled acrylonitrile. Nucleic acid, protein and lipid fractions will be isolated in binding site studies. Alterations induced by acrylonitrile in tissue glutathione concentrations would probably yield data on the importance of GSH as a binding site of acrylonitrile or its metabolites and as a protective nucleophile. The multidisciplinary approach, concentrating on general toxicity experiments, neuropathologic, endocrine and gastrointestinal lesions, carcinogenic action, and distribution of acrylonitrile will characterize the biologic action of the compound and further our understanding of the mechanism of action and public health implications of this important chemical.